KPCG_BOVIN
ID KPCG_BOVIN Reviewed; 682 AA.
AC P05128;
DT 13-AUG-1987, integrated into UniProtKB/Swiss-Prot.
DT 13-AUG-1987, sequence version 1.
DT 03-AUG-2022, entry version 187.
DE RecName: Full=Protein kinase C gamma type;
DE Short=PKC-gamma;
DE EC=2.7.11.13;
DE Flags: Fragment;
GN Name=PRKCG;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=3755548; DOI=10.1126/science.3755548;
RA Coussens L., Parker P.J., Rhee L., Yang-Feng T.L., Chen E.,
RA Waterfield M.D., Francke U., Ullrich A.;
RT "Multiple, distinct forms of bovine and human protein kinase C suggest
RT diversity in cellular signaling pathways.";
RL Science 233:859-866(1986).
RN [2]
RP REVIEW.
RX PubMed=3045562; DOI=10.1038/334661a0;
RA Nishizuka Y.;
RT "The molecular heterogeneity of protein kinase C and its implications for
RT cellular regulation.";
RL Nature 334:661-665(1988).
CC -!- FUNCTION: Calcium-activated, phospholipid- and diacylglycerol (DAG)-
CC dependent serine/threonine-protein kinase that plays diverse roles in
CC neuronal cells and eye tissues, such as regulation of the neuronal
CC receptors GRIA4/GLUR4 and GRIN1/NMDAR1, modulation of receptors and
CC neuronal functions related to sensitivity to opiates, pain and alcohol,
CC mediation of synaptic function and cell survival after ischemia, and
CC inhibition of gap junction activity after oxidative stress. Binds and
CC phosphorylates GRIA4/GLUR4 glutamate receptor and regulates its
CC function by increasing plasma membrane-associated GRIA4 expression. In
CC primary cerebellar neurons treated with the agonist 3,5-
CC dihyidroxyphenylglycine, functions downstream of the metabotropic
CC glutamate receptor GRM5/MGLUR5 and phosphorylates GRIN1/NMDAR1 receptor
CC which plays a key role in synaptic plasticity, synaptogenesis,
CC excitotoxicity, memory acquisition and learning. May be involved in the
CC regulation of hippocampal long-term potentiation (LTP), but may be not
CC necessary for the process of synaptic plasticity. May be involved in
CC desensitization of mu-type opioid receptor-mediated G-protein
CC activation in the spinal cord, and may be critical for the development
CC and/or maintenance of morphine-induced reinforcing effects in the
CC limbic forebrain. May modulate the functionality of mu-type-opioid
CC receptors by participating in a signaling pathway which leads to the
CC phosphorylation and degradation of opioid receptors. May also
CC contributes to chronic morphine-induced changes in nociceptive
CC processing. Plays a role in neuropathic pain mechanisms and contributes
CC to the maintenance of the allodynia pain produced by peripheral
CC inflammation. Plays an important role in initial sensitivity and
CC tolerance to ethanol, by mediating the behavioral effects of ethanol as
CC well as the effects of this drug on the GABA(A) receptors. During and
CC after cerebral ischemia modulate neurotransmission and cell survival in
CC synaptic membranes, and is involved in insulin-induced inhibition of
CC necrosis, an important mechanism for minimizing ischemic injury.
CC Required for the elimination of multiple climbing fibers during
CC innervation of Purkinje cells in developing cerebellum. Is activated in
CC lens epithelial cells upon hydrogen peroxide treatment, and
CC phosphorylates connexin-43 (GJA1/CX43), resulting in disassembly of
CC GJA1 gap junction plaques and inhibition of gap junction activity which
CC could provide a protective effect against oxidative stress.
CC Phosphorylates p53/TP53 and promotes p53/TP53-dependent apoptosis in
CC response to DNA damage. Involved in the phase resetting of the cerebral
CC cortex circadian clock during temporally restricted feeding. Stabilizes
CC the core clock component ARNTL/BMAL1 by interfering with its
CC ubiquitination, thus suppressing its degradation, resulting in phase
CC resetting of the cerebral cortex clock. {ECO:0000250|UniProtKB:P05129,
CC ECO:0000250|UniProtKB:P63318, ECO:0000250|UniProtKB:P63319}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.13;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.13;
CC -!- COFACTOR:
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU00041};
CC Note=Binds 3 Ca(2+) ions per subunit. The ions are bound to the C2
CC domain. {ECO:0000250|UniProtKB:P05129};
CC -!- ACTIVITY REGULATION: Classical (or conventional) PKCs (PRKCA, PRKCB and
CC PRKCG) are activated by calcium and diacylglycerol (DAG) in the
CC presence of phosphatidylserine. Three specific sites; Thr-499
CC (activation loop of the kinase domain), Thr-640 (turn motif) and Thr-
CC 659 (hydrophobic region), need to be phosphorylated for its full
CC activation.
CC -!- SUBUNIT: Interacts with CDCP1 and GRIA4. Interacts with TP53INP1 and
CC p53/TP53. Interacts with ARNTL/BMAL1. {ECO:0000250|UniProtKB:P05129,
CC ECO:0000250|UniProtKB:P63318, ECO:0000250|UniProtKB:P63319}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P63318}.
CC Cytoplasm, perinuclear region {ECO:0000250}. Cell membrane
CC {ECO:0000250|UniProtKB:P63318}; Peripheral membrane protein
CC {ECO:0000250}. Synapse, synaptosome {ECO:0000250|UniProtKB:P63318}.
CC Cell projection, dendrite {ECO:0000250|UniProtKB:P63319}.
CC Note=Translocates to synaptic membranes on stimulation.
CC {ECO:0000250|UniProtKB:P63318}.
CC -!- PTM: Autophosphorylation on Thr-659 appears to regulate motor functions
CC of junctophilins, JPH3 and JPH4. {ECO:0000250|UniProtKB:P63318}.
CC -!- PTM: Ubiquitinated. {ECO:0000250|UniProtKB:P05129}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. AGC Ser/Thr
CC protein kinase family. PKC subfamily. {ECO:0000305}.
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DR EMBL; M13976; AAA30704.1; -; mRNA.
DR PIR; C24664; KIBOGC.
DR RefSeq; NP_001159974.1; NM_001166502.2.
DR AlphaFoldDB; P05128; -.
DR SMR; P05128; -.
DR BioGRID; 159291; 1.
DR STRING; 9913.ENSBTAP00000018020; -.
DR PaxDb; P05128; -.
DR PRIDE; P05128; -.
DR GeneID; 282002; -.
DR KEGG; bta:282002; -.
DR CTD; 5582; -.
DR eggNOG; KOG0696; Eukaryota.
DR HOGENOM; CLU_000288_54_2_1; -.
DR InParanoid; P05128; -.
DR OrthoDB; 614710at2759; -.
DR Proteomes; UP000009136; Unplaced.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0030425; C:dendrite; ISS:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0045202; C:synapse; IEA:UniProtKB-SubCell.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004698; F:calcium-dependent protein kinase C activity; IEA:UniProtKB-EC.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IBA:GO_Central.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0035556; P:intracellular signal transduction; IBA:GO_Central.
DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; ISS:UniProtKB.
DR GO; GO:1901799; P:negative regulation of proteasomal protein catabolic process; ISS:UniProtKB.
DR GO; GO:0031397; P:negative regulation of protein ubiquitination; ISS:UniProtKB.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IBA:GO_Central.
DR GO; GO:0042752; P:regulation of circadian rhythm; ISS:UniProtKB.
DR GO; GO:0032095; P:regulation of response to food; ISS:UniProtKB.
DR GO; GO:0043278; P:response to morphine; ISS:UniProtKB.
DR GO; GO:0048265; P:response to pain; ISS:UniProtKB.
DR GO; GO:0048511; P:rhythmic process; IEA:UniProtKB-KW.
DR CDD; cd00029; C1; 2.
DR Gene3D; 2.60.40.150; -; 1.
DR InterPro; IPR000961; AGC-kinase_C.
DR InterPro; IPR046349; C1-like_sf.
DR InterPro; IPR000008; C2_dom.
DR InterPro; IPR035892; C2_domain_sf.
DR InterPro; IPR020454; DAG/PE-bd.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR002219; PE/DAG-bd.
DR InterPro; IPR017892; Pkinase_C.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR014375; Protein_kinase_C_a/b/g.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR Pfam; PF00130; C1_1; 2.
DR Pfam; PF00168; C2; 1.
DR Pfam; PF00069; Pkinase; 1.
DR Pfam; PF00433; Pkinase_C; 1.
DR PIRSF; PIRSF000550; PKC_alpha; 1.
DR PRINTS; PR00360; C2DOMAIN.
DR PRINTS; PR00008; DAGPEDOMAIN.
DR SMART; SM00109; C1; 2.
DR SMART; SM00239; C2; 1.
DR SMART; SM00133; S_TK_X; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF49562; SSF49562; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR SUPFAM; SSF57889; SSF57889; 2.
DR PROSITE; PS51285; AGC_KINASE_CTER; 1.
DR PROSITE; PS50004; C2; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
DR PROSITE; PS00479; ZF_DAG_PE_1; 2.
DR PROSITE; PS50081; ZF_DAG_PE_2; 2.
PE 2: Evidence at transcript level;
KW ATP-binding; Biological rhythms; Calcium; Cell membrane; Cell projection;
KW Cytoplasm; Kinase; Membrane; Metal-binding; Nucleotide-binding;
KW Phosphoprotein; Reference proteome; Repeat;
KW Serine/threonine-protein kinase; Synapse; Synaptosome; Transferase;
KW Ubl conjugation; Zinc; Zinc-finger.
FT CHAIN <1..682
FT /note="Protein kinase C gamma type"
FT /id="PRO_0000055688"
FT DOMAIN 142..260
FT /note="C2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT DOMAIN 336..599
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 600..670
FT /note="AGC-kinase C-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00618"
FT ZN_FING 20..70
FT /note="Phorbol-ester/DAG-type 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00226"
FT ZN_FING 85..135
FT /note="Phorbol-ester/DAG-type 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00226"
FT ACT_SITE 465
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 171
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P05129"
FT BINDING 172
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P05129"
FT BINDING 172
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P05129"
FT BINDING 178
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P05129"
FT BINDING 231
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P05129"
FT BINDING 231
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P05129"
FT BINDING 232
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P05129"
FT BINDING 233
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P05129"
FT BINDING 233
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P05129"
FT BINDING 233
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:P05129"
FT BINDING 236
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:P05129"
FT BINDING 237
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:P05129"
FT BINDING 239
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P05129"
FT BINDING 239
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:P05129"
FT BINDING 342..350
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 365
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 235
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 305
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P63318"
FT MOD_RES 307
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P63318"
FT MOD_RES 311
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P63318"
FT MOD_RES 313
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P63318"
FT MOD_RES 315
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P63318"
FT MOD_RES 317
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P63318"
FT MOD_RES 358
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P63318"
FT MOD_RES 499
FT /note="Phosphothreonine; by PDPK1"
FT /evidence="ECO:0000250|UniProtKB:P63318"
FT MOD_RES 633
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000255"
FT MOD_RES 640
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P63318"
FT MOD_RES 659
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P63318"
FT MOD_RES 660
FT /note="Phosphotyrosine; by SYK"
FT /evidence="ECO:0000250"
FT MOD_RES 672
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P63319"
FT NON_TER 1
SQ SEQUENCE 682 AA; 77156 MW; 20392D11188C731C CRC64;
RPLFCRKGAL RQKVVHEVKS HKFTARFFKQ PTFCSHCTDF IWGIGKQGLQ CQVCSFVVHR
RCHEFVTFEC PGAGKGPQTD DPRNKHKFRL HSYSSPTFCD HCGSLLYGLV HQGMKCSCCE
MNVHRRCVRS VPSLCGVDHT ERRGRLQLEI RAPTSDEIHV TVGEARNLIP MDPNGLSDPY
VKLKLIPDPR NLTKQKTRTV KATLNPVWNE TFVFNLKPGD VERRLSVEVW DWDRTSRNDF
MGAMSFGVSE LLKAPVDGWY KLLNQEEGEY YNVPVADADN CNLLQKFEAC NYPLELYERV
RTGPSSSPIP SPSPSPTDSK RCFFGASPGR LHISDFSFLM VLGKGSFGKV MLAERRGSDE
LYAIKILKKD VIVQDDDVDC TLVEKRVLAL GGRGPGGRPH FLTQLHSTFQ TPDRLYFVME
YVTGGDLMYH IQQLGKFKEP HAAFYAAEIA IGLFFLHNQG IIYRDLKLDN VMLDAEGHIK
ITDFGMCKEN VFPGSTTRTF CGTPDYIAPE IIAYQPYGKS VDWWSFGVLL YEMLAGQPPF
DGEDEEELFQ AIMEQTVTYP KSLSREAVAI CKGFLTKHPA KRLGSGPDGE PTIRAHGFFR
WIDWDRLERL EIAPPFRPRP CGRSGENFDK FFTRAAPALT PPDRLVLASI DQAEFQGFTY
VNPDFVHPDA RSPISPTPVP VM
